rocbrutinib (LP-168) / Lupeng Pharma, Jiangsu Hansoh Pharma - LARVOL DELTA

Efficacy and safety of rocbrutinib, the fourth generation bruton's tyrosine kinase inhibitor, in patients with BTK inhibitor pre-treated relapsed or refractory Mantle Cell Lymphoma: Results from a Phase II rock-1 trial (ASH 2025) - P2 | "The high ORR (63.9%) and prolonged DOR(median 16.46 months) observed in this trial, coupled with a low incidence of BTKi-associated toxicities,position rocbrutinib as a promising therapeutic option for this difficult-to-treat population. The clinicalbenefit of rocbrutinib in patients with MCL will be further confirmed in randomized phase III studies."

Clinical • P2 data • Atrial Fibrillation • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • Thrombocytopenia

Efficacy and safety of rocbrutinib, a highly selective 4th-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory Mantle Cell Lymphoma (R/R MCL): Updated results from the phase 1 study (ASH 2025) - P1 | "The18-month PFS rate was 74.3%. ConclusionConsistent with previously reported data in patients with post BTKi R/R MCL, rocbrutinib demonstrates afavorable safety profile and robust efficacy in patients with BTKi naïve R/R MCL, with high response rates,deep remissions, and durable responses."

Clinical • P1 data • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hypertension • Lymphoma • Mantle Cell Lymphoma

Efficacy and safety of rocbrutinib, a highly selective 4th-generation BTK inhibitor, in Chinese patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (ASH 2025) - P1 | "2 patients with BTKL528W mutationachieved PR and are still on treatment (DOR: 8.1 and 14.0 months).After median follow-up of 7.4 months, all 12 1L patients remained on treatment. In the R/R BTKi naivepopulation (median follow-up 15.8 months), the estimated 12-month PFS rate as 94.1% (95% CI: 65.0-99.1); In the R/R post-BTKi population (median follow-up 15.5 months), the estimated 12-month PFS rateas 83.3% (95% CI: 48.2-95.6).ConclusionRocbrutinib has a favorable safety profile and shows durable responses in patients with CLL/SLL,including those with prior BTK inhibitor exposure and/or with covalent and noncovalent BTKi-resistantmutations."

Clinical • IO biomarker • Atrial Fibrillation • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • TP53

Targeting BTKi-resistant CLL using the dual irreversible/reversible 4th generation BTK inhibitor rocbrutinib (ASH 2025) - P1 | "UsingFPCBA, rocbrutinib was the only BTKi—among ibrutinib, acalabrutinib, zanubrutinib, nemtabrutinib, andpirtobrutinib—to retain nanomolar potency against WT BTK as well as clinically relevant resistancemutations, including C481S, V416L, M437R, and L528W. Collectively, our findings demonstrate rocbrutinib is a potent and selective inhibitor of BTKwith activity even in the presence of mutations that mediate resistance to cBTKi and ncBTKi. These datasupport the continued investigation of rocbrutinib, which is currently being studied in the phase 1 settingof CLL and NHL (NCT04775745 and NCT04993690)."

Chronic Lymphocytic Leukemia • CCL3 • PLCG2

Updates of R/R CLL with prior exposure to Bruton's tyrosine kinase (BTK) inhibitor and/or bcl-2 inhibitor in the Phase 1 trial of LP-168 (Rocbrutinib), a novel COVALENT and non-COVALENT BTK inhibitor (ASH 2025) - P1, P2 | "R/R CLL that has been treated with prior BTKi and/or Bcl-2 inhibitor, such as venetoclax, remains an unmet need in resistant CLL despite pirtobrutinib'saccelerated approval. Encouraging safety and efficacy are observed in the population exposed to BTKi (includingboth cBTKi and ncBTKi) and/or Bcl-2i. Rocbrutinib could be a potential therapy for double or triple-exposed CLL patients who currently have limited treatment options."

IO biomarker • P1 data • Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Constipation • Cough • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hypertension • Infectious Disease • Musculoskeletal Pain • Nephrology • Neutropenia • Novel Coronavirus Disease • Otorhinolaryngology • Pneumonia • Renal Cell Carcinoma • Renal Disease • Respiratory Diseases • Septic Shock • Sinusitis • Solid Tumor • BTK • IGH • PLCG2 • TP53

Genome-Wide CRISPR/Cas9 Knockout Screen Reveals Novel LP-168 (Rocbrutinib) Combinations Targeting BCL-2 Protein Members for Chronic Lymphocytic Leukemia (ASH 2024) - "As BCL-2 interacts with both pathways, and was amongst the top-ranking genes depleted, we chose to target it with either venetoclax (BCL-2i) or with LP-118, a dual BCL-2/-xL inhibitor currently under investigation for R/R hematological malignancies. Conclusions : These data show combined use of LP-168 with pharmacological inhibitors targeting BCL-2 and BCL-xL display synergistic activity in CLL, even in the presence of mutations that mediate resistance to BTKi and BCL-2i. These data are consistent with clinical data showing dual targeting of BTK, with previous generation inhibitors, and BCL-2 has been effective in the clinic, with many patients achieving uMRD and prolonged remission off therapy and supports continued preclinical and future clinical investigation of LP-168 with inhibitors of BCL-2 and BCL-2/-xL."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • BCL2 • BCL2L1

LP-168 (Rocbrutinib), a Novel Covalent and Non-Covalent Next-Generation Inhibitor of Bruton's Tyrosine Kinase: Updates on the Phase 1 Trial and Initial Results of the CLL Gatekeeper Mutation Cohort (ASH 2024) - P1 | "Preliminary encouraging efficacy is observed in this GM cohort, including those treated with one or more BTKi such as pirtobrutinib and nemtabrutinib. Rocbrutinib could potentially fill an unmet need in CLL for pts with resistant CLL. Ongoing and future clinical trials will focus on dose optimization and combination studies."

P1 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Constipation • Cough • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • PLCG2 • TP53

Safety and Efficacy of Rocbrutinib in Patients with Relapsed/Refractory Marginal Zone Lymphoma (ASH 2024) - P1 | "Conclusion : Rocbrutinib is well tolerated and has shown promising anti-tumor activity in terms of response rate in patients with R/R MZL. Longer follow-up is needed to assess the long-term benefit."

Clinical • Extranodal Marginal Zone Lymphoma • Hematological Disorders • Hematological Malignancies • Hypotension • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

Rocbrutinib, a New-Generation BTK Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Non-GCB Diffuse Large B Cell Lymphoma (ASH 2024) - P1 | "Based on the encouraging data, rocbrutinib has received breakthrough therapy designation for the treatment of patients with non-GCB DLBCL who have received at least 2 lines of prior therapies from China CDE (center of drug evaluation). A Phase 1b study of rocbrtuinib in combination with R-CHOP for untreated non-GCB DLBCL is also ongoing (NCT06251180)."

Clinical • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Dyslipidemia • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Thrombocytopenia

Targeting BTKi-Resistant CLL Using the Dual Irreversible/Reversible 4th Generation BTK Inhibitor Rocbrutinib (IWCLL 2025) - P1 | "Using FPCBA, rocbrutinib was the only BTKi—among ibrutinib, acalabrutinib, zanubrutinib, nemtabrutinib, and pirtobrutinib—to retain nanomolar potency against WT BTK as well as clinically relevant resistance mutations, including C481S, V416L, M437R, and L528W. Collectively, our findings demonstrate rocbrutinib is a potent and selective inhibitor of BTK with activity even in the presence of mutations that mediate resistance to cBTKi and ncBTKi. These data support the continued investigation of rocbrutinib, which is currently being studied in the phase 1 setting of CLL and NHL (NCT04775745 and NCT04993690)."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • BCL2 • BCL2A1 • BCL2L1 • CCL3 • CD40 • PLCG2

Targeting BTKi-Resistant CLL Using the Dual Irreversible/Reversible 4th Generation BTK Inhibitor Rocbrutinib (IWCLL 2025) - P1 | "Using FPCBA, rocbrutinib was the only BTKi—among ibrutinib, acalabrutinib, zanubrutinib, nemtabrutinib, and pirtobrutinib—to retain nanomolar potency against WT BTK as well as clinically relevant resistance mutations, including C481S, V416L, M437R, and L528W. Collectively, our findings demonstrate rocbrutinib is a potent and selective inhibitor of BTK with activity even in the presence of mutations that mediate resistance to cBTKi and ncBTKi. These data support the continued investigation of rocbrutinib, which is currently being studied in the phase 1 setting of CLL and NHL (NCT04775745 and NCT04993690)."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • BCL2 • BCL2A1 • BCL2L1 • CCL3 • CD40 • PLCG2

A Study of Rocbrutinib in Participants With Relapse or Refractory Non-GCB Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.

Monotherapy • New P2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Lupeng Pharmaceutical's BTK inhibitor is planned to be included in the priority review [Google translation] (PhIRDA) - "On May 8, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that the rocbrutinib tablets applied by Lupeng Pharmaceuticals are planned to be included in the priority review, which is suitable for adult mantle cell lymphoma (MCL) patients who have previously received Bruton's tyrosine kinase (BTK) inhibitor treatment....Based on the safety and efficacy data of LP-168 obtained in the Phase 1 study, the CDE agreed to use the ROCK-1 study as a pivotal registration study to support the conditional marketing application of LP-168 in the target population."

Priority review • Mantle Cell Lymphoma

LP-168-CN301: Phase Ib Study of Rocbrutinib in Combination with R-CHOP in Patients with Newly Diagnosed B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=112 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Hansoh Pharmaceuticals cooperated with BTK inhibitor for over 720 million yuan, and the clinical trial was approved again [Google translation] (163.com) - "On February 25, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that the Class 1 new drug HS-10561 capsules applied by Hansoh Pharmaceuticals were approved for clinical trials and are intended to be developed to treat chronic spontaneous urticaria....The clinical approval of HS-10561 capsule for CSU indication means that it will soon conduct clinical research on CSU indication."

New trial • Chronic Spontaneous Urticaria • Immunology

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HS-10561 Capsule in Healthy Chinese Adults and Patients With Chronic Spontaneous Urticaria. (clinicaltrials.gov) - P1/2 | N=150 | Not yet recruiting | Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

New P1/2 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Study of Rocbrutinib in Participants with Relapse or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=62 | Active, not recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

【ASH 2024】Lupeng Pharmaceuticals’ new generation BTK inhibitor Rocbrutinib (Lobutinib) research data continues to update [Google translation] (bydrug.pharmcube.com) - "After the first announcement of research data at the 2023 ASH Annual Meeting, Rocbrutinib...continued to update the latest data of clinical and non-clinical studies in China and the United States in the form of posters...Content highlights: i) Focus on updating the data from the DLBCL cohort of the Chinese LP-168-CN101 Phase I clinical study (NCT04993690). ii) The US Phase I clinical study LP-168-US-I-01 (NCT04775745) updated the ORR (objective response rate) data of the Rocbrutinib cohort in chronic lymphocytic leukemia (CLL) with T474 mutation after treatment with BTK inhibitors, which is expected to fill the treatment needs of patients with drug-resistant CLL."

P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Lymphoma • Marginal Zone Lymphoma

A Study of Rocbrutinib in Participants with Relapse or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=62 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Trial primary completion date: Feb 2024 ➔ Dec 2024

Monotherapy • Trial primary completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

A Study of LP-168 in Participants with Relapse or Refractory B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Novel BTK Inhibitor LP-168 Under Investigation in China for R/R Mantle Cell Lymphoma (OncLive) - "The highly selective next-generation BTK inhibitor LP-168 is currently being investigated in the phase 2 ROCK-1 trial (NCT05716087), an open-label, single-arm, multicenter investigation evaluating the safety and efficacy of the agent given as monotherapy in the treatment of patients with relapsed/refractory mantle cell lymphoma...ROCK-1 is enrolling patients with MCL who present with a measurable lesion and have been previously treated with a covalent BTK inhibitor...Investigators will enroll 62 patients who meet the aforementioned criteria, and all patients will receive oral LP-168 at 150 mg once per day...The first patient was enrolled onto the ROCK-1 clinical trial on May 12, 2023, in China, and at present, there are 41 study sites across the country actively enrolling patients."

Enrollment status • Mantle Cell Lymphoma

An open label, single arm, multicenter phase II study of the efficacy and safety of LP-168 monotherapy for relapsed or refractory mantle cell lymphoma. (ASCO 2024) - P2 | "Currently 41 study sites across China are actively enrolling patients. ClinicalTrials.gov Identifier: NCT05716087."

Clinical • Monotherapy • P2 data • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Oncology • Targeted Protein Degradation • CYP3A4

LP-168-CN301: Phase Ib Study of Rocbrutinib in Combination With R-CHOP in Patients With Newly Diagnosed B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=112 | Recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The Mass Balance Study of LP-168 in Healthy Subjects (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Active, not recruiting ➔ Completed

Trial completion

The Mass Balance Study of LP-168 in Healthy Subjects (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. | Recruiting ➔ Active, not recruiting

Enrollment closed